1. Field of the Invention
This invention relates, generally, to ion mobility spectrometer analysis. More specifically, it relates to algorithms to approximate a solution to a momentum transfer cross section of an analyte in a buffer gas as measured by an ion mobility spectrometer.
2. Brief Description of the Prior Art
Ion mobility spectrometry (IMS) has been used for structural characterization of generally small organic and inorganic molecules. Recent advancement in the field have led to equipment modifications that allow IMS to be used for research involving large, macromolecular organic and biological compounds. IMS has shown particular usefulness in identifying macromolecular compounds related to a variety of illnesses and diseases. However, structure-elucidation of the compounds through IMS by comparison of IMS results of collision cross-sections with known, model molecular structures requires time-consuming and resource-intensive algorithms.
Several methods exist to approximate a solution to a momentum transfer cross section of an analyte in a buffer gas as measured by an ion mobility spectrometer in the low-field regime. However, none of the known methods combine low computational demand while providing a solution with a high degree of accuracy while also being adaptable for a plurality of drift gases. Four of the primary existing methods are described below.
The Trajectory Method (TM) simplifies the scattering problem by approximating the scattering potential energy surface by a sum of two-body interaction terms. The value of the momentum transfer cross section is then obtained by solving the Langrangian equations for a sufficiently large number of collision geometries on the potential energy surface and deducing the corresponding deflection angles. However, the scattering process of polyatomic ions in the drift cell is a many-body problem and exceedingly difficult to solve. Consequently, the computational demands to obtain a momentum transfer cross section for biological macromolecules are tremendous, and thus not applicable into high-throughput or molecular modeling software.
The Exact Hard Sphere Scattering (EHSS) approximation simplifies the two-body interaction potential to that of the collision of hard spheres with defined collision radius Rcoll. The momentum transfer cross section is then obtained via ray tracing of the scattered trajectories and deducing the corresponding deflection angles. This method is not accurate enough for reliable assignment of molecular structure (due to the hard-sphere collision approximation), and further too time consuming for application into a high-throughput or molecular modeling software (due to the usage of ray tracing).
The Projection Approximation (PA) simplifies the scattering process by ignoring any interaction between the buffer gas and the analyte. Instead, it approximates the momentum transfer cross section as the orientation averaged area by determining the area enclosed by the analyte's atoms projected onto a plane for a plurality of orientations. This method is fast enough for incorporation into an automatic, high-throughput or molecular modeling software, but it's predicted values include errors of up to 20-30 percent due to neglect of buffer gas-analyte interactions, and thus is useless for structure assignment.
In the framework of the Projection Superposition Approximation (PSA), molecular collision cross-sections are computed as a projection approximation that is modified to account for buffer gas-analyte interactions and correct for shape-effects through a shape factor. It is consequently very accurate, but not as fast as necessary to be useful for incorporation into automated, structure-assignment software. Furthermore, this method ignores the molecular charge distribution and recent attempts to parameterize this method for nitrogen have shown that due to this approximation the predicted momentum transfer cross sections can be unreliable if the buffer gas is polarizable. It is anticipated that this method is therefore also unreliable for use with other strongly interacting drift gases, such as carbon monoxide or carbon dioxide.
Accordingly, what is needed is an algorithm to approximate a solution to a momentum transfer cross section of an analyte in a buffer gas as measured by an ion mobility spectrometer in the low-field regime that combines low computational demand while providing a solution with a high degree of accuracy while also being adaptable for a plurality of drift gases. However, in view of the art considered as a whole at the time the present invention was made, it was not obvious to those of ordinary skill in the field of this invention how the shortcomings of the prior art could be overcome.
All referenced publications are incorporated herein by reference in their entirety. Furthermore, where a definition or use of a term in a reference, which is incorporated by reference herein, is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
While certain aspects of conventional technologies have been discussed to facilitate disclosure of the invention, Applicants in no way disclaim these technical aspects, and it is contemplated that the claimed invention may encompass one or more of the conventional technical aspects discussed herein.
The present invention may address one or more of the problems and deficiencies of the prior art discussed above. However, it is contemplated that the invention may prove useful in addressing other problems and deficiencies in a number of technical areas. Therefore, the claimed invention should not necessarily be construed as limited to addressing any of the particular problems or deficiencies discussed herein.
In this specification, where a document, act or item of knowledge is referred to or discussed, this reference or discussion is not an admission that the document, act or item of knowledge or any combination thereof was at the priority date, publicly available, known to the public, part of common general knowledge, or otherwise constitutes prior art under the applicable statutory provisions, or is known to be relevant to an attempt to solve any problem with which this specification is concerned.